DESCRIPTION (Adapted from abstract): The thalamus and neocortex are essential for normal sensation, movement and cognition, and they work in intimate, inextricable association. The thalamus is the origin of virtually all specific information entering the neocortex, and the neocortex in turn sends massive feedback to the thalamus. This bidirectional communication occurs via parallel thalamo-cortical-thalamic loops. Thalamocortical properties are not uniform and fixed, but can change rapidly during various behavioral states and during stages of sleep. The characteristics and cellular mechanisms of these state transitions are poorly understood, but they critically important for a variety of cognitive processes. The goal of this project is to investigate the synapses that interconnect the thalamus and neocortex, and neurons within the neocortex, and understand their short-term dynamics and sensitivity to presynaptic neuromodulators. Measurements of synaptic efficacy, short-term plasticity, release properties, cellular specificity, and neuromodulator sensitivity will be made in the rat and mouse somatosensory system, both in vitro and in vivo. The overarching hypothesis is that each synapse type has distinctive characteristics, adapted to its specific needs and flexible enough for different conditions. Secondarily we want to know how synaptic functions measured in vitro compare with those measured in vivo. The results will provide the first detailed functional data on the major synaptic elements in a system of parallel thalamo-cortico-thalamic pathways. The information will be important for understanding the mechanisms of information processing in the forebrain, and the neurochemical control of behavioral states and forebrain pathologies.